A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Chronic Lymphocytic Leukemia Clinical Trial

— BRUIN-CLL-314  

Official title:

A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05254743
• Other study ID #: 18281
• Secondary ID: J2N-OX-JZNULOXO-
• Status: Recruiting
• Phase: Phase 3
• Start date: July 22, 2022
• Est. completion date: August 2028

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: There may be multiple sites in this clinical trial. 1-877-CTLILL
• Phone: 1-317-615-4559
• Email: ClinicalTrials.gov[@]lilly.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL. Participants may or may not have already had treatment for their cancer. Participation could last up to six years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 650
• Est. completion date: August 2028
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Adequate organ function
• Platelets greater than or equal to (=)50 x 10?/liter (L) or =30 x 10?/L in participants with documented bone marrow involvement considered to impair hematopoiesis,
• Hemoglobin =8 grams/deciliter (g/dL) or =6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
• Absolute neutrophil count =0.75 x 10?/L or =0.50 × 10?/L in participants with documented bone marrow involvement considered to impair hematopoiesis
• Kidney function: Estimated creatinine clearance =30 milliliters per minute (mL/min)

Exclusion Criteria:

• Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment
• Known or suspected central nervous system (CNS) involvement
• A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease
• Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
• Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter
• Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
• Active cytomegalovirus (CMV) infection
• Active uncontrolled systemic bacterial, viral, or fungal infection
• Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
• Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments
• Ongoing inflammatory bowel disease
• Prior exposure to BTK inhibitor (covalent or noncovalent)
• Concurrent use of investigational agent or anticancer therapy except hormonal therapy
• Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
• Use of = 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug
• Vaccination with a live vaccine within 28 days prior to randomization
• Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment
• Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, B-cell
• Leukemia, Lymphocytic
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• Pirtobrutinib
Administered orally.
• Ibrutinib
Administered orally.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	ABB	Ciudad Autónoma De Buenos Aire
Argentina	Instituto Alexander Fleming	Ciudad Autonoma Buenos Aires
Argentina	Hospital Privado De Comunidad	Mar Del Plata	Buenos Aires
Argentina	Clínica de Nefrología, Urología y Enfermedades Cardiovasculares	Santa Fe
Australia	One Clinical Research	Nedlands	Western Australia
Australia	Sunshine Hospital	St Albans	Victoria
Australia	The Perth Blood Institute	West Perth
Austria	Ordensklinikum Linz	Linz	Oberösterreich
Austria	Hanusch Krankenhaus	Vienna
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Belgium	AZ Delta	Roeselare	West Flanders
Belgium	VITAZ	Sint-Niklaas	Oost-Vlaanderen
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos	São Paulo
Brazil	UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu	Botucatu	Sao Paulo
Brazil	Centro de Hematologia e Hemoterapia - Hemocentro de Campinas - UNICAMP	Campinas	Sao Paulo
Brazil	Hospital Uopeccan - Centro de Pesquisa Clinica	Cascavel
Brazil	Centro Integrado de Oncologia de Curitiba	Curitiba	Paraná
Brazil	Hospital Erasto Gaertner - Liga Paranaense de Combate ao Câncer	Curitiba	Paraná
Brazil	Instituto do Câncer - Hospital São Vicente de Paulo	Passo Fundo	Rio Grande Do Sul
Brazil	Centro Gaucho Integrado de Oncologia, Hematologia, Ensino e Pesquisa - Hospital Mae de Deus	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (USP) - HCFMRP	Ribeirão Preto	São Paulo
Brazil	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo André	São Paulo
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	Sao Jose Rio Preto	Sao Paulo
Brazil	Hospital Beneficência Portuguesa de São Paulo	Sao Paulo
Brazil	Hospital Santa Marcelina	Sao Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina da USP	São Paulo
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Hopital de L'Enfant Jesus	Québec
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Chile	Centro de Estudios Clinicos SAGA	Providencia	Santiago
Chile	CeCim Biocinetic	Santiago	Región Metropolitana
Chile	Sociedad de Investigaciones Médicas Limitada	Temuco	IX Región
Chile	Centro de Investigaciones Clínicas Viña del Mar (CIC)	Viña del Mar	Valparaíso
China	Hunan Cancer Hospital	Changsha	Hunan
China	The 2nd Xiangya Hospital of Central South University	Changsha	Hunan
China	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Hainan General Hospital	Haikou
China	First Affiliated Hosp of College of Med, Zhejiang University	Hangzhou
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The Second Hospital of Anhui Medical University	Hefei	Anhui
China	Jiangxi Provincial Cancer Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Blood Institute of the Chinese Academy of Medical science	Tianjin	Tianjin
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	The Affiliated Cancer Hospital of Xinjiang Medical university	Urumqi	Xinjiang
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan
China	Wu Han Tongji Hospital	Wuhan City	Hubei
China	The Fourth Affiliated Hospital Zhejiang University School of Medicine	Yiwu	Zhejiang
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni Nemocnice Ostrava	Ostrava-Poruba
Czechia	Fakultni Nemocnice Plzen	Plzen - Lochotin
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	CHD Vendee	La Roche sur Yon
France	Centre Hospitalier du Mans	Le Mans
France	Centre Hospitalier Universitaire (Limoges) (CHU DUPUYTREN 1)	Limoges
France	CHU de Nantes - Hotel Dieu	Nantes	Cedex 1
France	Centre Antoine Lacassagne	Nice	Nice Cedex 2
France	Hopital de la Pitie Salpetriere	Paris	Cedex 13
France	Centre Hospitalier Lyon Sud	Pierre Benite	Cedex
France	Hôpital de Pontchaillou	Rennes	Cedex 9
France	Centre Henri Becquerel	Rouen Cedex
France	CHRU De Tours	Tours	Tours Cedex 9
Germany	GEFOS (Gesellschaft für onkologische Studien) Dortmund mbH	Dortmund	Nordrhein Westfalen
Germany	Gemeinschaftspraxis Haematologie und Onkologie	Dresden	Sachsen Anhalt
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden	Sachsen
Germany	Uniklinik Köln	Kerpener	Köln
Germany	Universitaetsklinikum Ulm	Ulm	Baden
Hungary	Debreceni Egyetem	Debrecen
Hungary	Markusovszky Egyetemi Oktatokorhaz	Szombathely
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center-Beilinson Campus	Petach-Tikva
Israel	Chaim Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi IRCCS	Bologna
Italy	Fondazione del Piemonte per l'Oncologia IRCCS Candiolo	Candiolo	Torino
Italy	IRCCS Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori "Dino Amadori" - IRST	Meldola	Forlì-Cesena
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Unita Sanitaria Locale di Reggio Emilia	Reggio Emilia
Italy	A.O.U. Citta' della Salute e della Scienza di Torino	Torino	Otago
Italy	Centro Ricerche Cliniche di Verona s.r.l.	Verona
Japan	Tokai University Hospital- Isehara Campus	Isehara	Kanagawa
Japan	Kumamoto University Hospital	Kumamoto
Japan	Yamagata University Hospital	Yamagata
Korea, Republic of	Inje Univ Busan Paik Hospital	Busan
Korea, Republic of	The Catholic University of Korea-Seoul St. Mary's Hospital	Seocho-Gu	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul, Korea
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Waikato Hospital	Hamilton
New Zealand	P3 Research	Newtown	Wellington
New Zealand	Middlemore Hospital	Otahuhu
Poland	KO-MED Centra Kliniczne	Biala Podlaska
Poland	Szpital Uniwersytecki nr 2 im. dr Jana Biziela w BydgoszczyKlinika Hematologii	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia MCM Krakow	Krakow
Poland	Klinika Hematoonkologii i Transplantacji Szpiku	Lublin
Poland	Szpital Wojewodzki w Opolu	Opole
Poland	Centrum Medyczne Pratia Poznan	Skorzewo	Poznan
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu Klinika Hematologii	Wroclaw
Spain	Hospital Germans Trias i Pujol	Badalona	Catalunya [Cataluña]
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Cataluña
Spain	Institut Català d'Oncologia de Girona (ICO Girona)	Girona	Cataluna
Spain	Hospital Duran i Reynals	L'Hospitalet de Llobregat
Spain	Hospital De Gran Canaria Dr. Negrin	Las Palmas de Gran Canaria
Spain	Clinica Universitaria De Navarra	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid, Comunidad De
Spain	Hospital Costa Del Sol	Marbella	Malaga
Spain	Hospital De Navarra	Pamplona	Navarra
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Taiwan	Chang Bing Show Chwan Memorial Hospital	Changhua
Taiwan	Chang Gung Memorial Hospital - Chiayi	Putz	Chiayi Hsien
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Koo Foundation Sun Yan-Sen Cancer Center	Taipei
Turkey	Gazi University Faculty of Medicine	Ankara	Yenimahalle
Turkey	9 Eylul University Hospital	Balçova	Izmir
Turkey	Ege University Medical Faculty	Bornova	Izmir
Turkey	Acibadem Maslak Hastanesi	Istanbul
Turkey	Istanbul University Istanbul Medical Faculty	Istanbul
Turkey	Koc University American Hospital	Istanbul
Turkey	Ankara University Medicine Hospital	Mamak	Ankara
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	Bristol, City Of
United Kingdom	Castle Hill Hospital	Hull	East Riding Of Yorkshire
United Kingdom	Leicester Royal Infirmary	Leicester	Leicestershire
United Kingdom	St Bartholomew's Hospital	London	London, City Of
United Kingdom	Singleton Hospital	Swansea
United States	Pacific Cancer Medical Center, Inc	Anaheim	California
United States	Hematology Oncology Clinic	Baton Rouge	Louisiana
United States	Alta Bates Summit Medical Center	Berkeley	California
United States	American Oncology Partners of Maryland, PA	Bethesda	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Asclepes Research Centers Florida	Brooksville	Florida
United States	TOI Clinical Research	Cerritos	California
United States	Novant Cancer Institute Charlotte	Charlotte	North Carolina
United States	Sarah Cannon Research Institute SCRI	Chattanooga	Tennessee
United States	The James Cancer Hospital	Columbus	Ohio
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Prisma Health Cancer Institute	Greenville	South Carolina
United States	Westchester Medical Center	Hawthorne	New York
United States	Genesis Cancer Center	Hot Springs	Arkansas
United States	Houston Methodist Hospital Cancer Center	Houston	Texas
United States	Kelsey Research Foundation	Houston	Texas
United States	Cancer Specialists of North Florida -St Augustine	Jacksonville	Florida
United States	Lumi Research	Kingwood	Texas
United States	Lakeland Regional Health Systems Inc	Lakeland	Florida
United States	Baptist Healthcare System, Inc.	Louisville	Kentucky
United States	Tulane Cancer Center Office of Clinical Research	New Orleans	Louisiana
United States	Eastern Connecticut Hematology/Oncology Assoc.	Norwich	Connecticut
United States	Stanford School of Medicine-Cancer Clinical Trials Office	Palo Alto	California
United States	Lifespan Cancer Institute	Providence	Rhode Island
United States	Eisenhower Army Medical Center	Rancho Mirage	California
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Baylor Scott & White Health	Round Rock	Texas
United States	Florida Cancer Specialists	Saint Petersburg	Florida
United States	TidalHealth Peninsula Regional, Inc.	Salisbury	Maryland
United States	Sharp Memorial Hospital	San Diego	California
United States	California Cancer Associates for Research and Excellence	San Marcos	California
United States	Summit Cancer Care, P.C.	Savannah	Georgia
United States	MultiCare Health System Institute for Research and Innovation	Spokane	Washington
United States	Summit Cancer Treatment Center	Spokane	Washington
United States	Florida Cancer Specialists East	West Palm Beach	Florida
United States	Cancer Care Associates of York	York	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Loxo Oncology, Inc.	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR)	ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria	Baseline to best overall response at or before the initiation of subsequent anti-cancer therapy (if any) (approximately 3 years and 5 months)
Secondary	Event-Free Survival (EFS)	EFS by IRC per iwCLL 2018 criteria	Randomization to first occurrence of treatment discontinuation due to adverse event/toxicity, treatment-emergent atrial fibrillation or atrial flutter of any grade, progressive disease (PD) or death (approximately 4 years)
Secondary	Progression-Free Survival (PFS)	PFS by IRC per iwCLL 2018 criteria	Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months)
Secondary	Duration of Response (DOR)	DOR	Time from the date of the first documented response of CR, CRi, nPR or PR to the earlier of documentation of definitive PD (per iwCLL 2018 criteria) or death from any cause (approximately 2 years)
Secondary	Overall Survival (OS)	OS	Randomization to death from any cause (approximately 6 years)
Secondary	Time to Next Treatment (TTNT)	TTNT	Randomization to initiation of the next systemic anticancer therapy for CLL/SLL or death from any cause, whichever occurs first (approximately 6 years)
Secondary	Time to Worsening (TTW) of CLL/SLL Related Symptoms	Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.	Randomization to time to worsening symptoms (approximately 6 years)

External Links

•   A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-314)